The goal of this investigation is to determine how the structure and composition of lipids and/or proteins in real and model lipoproteins regulate (1) the binding of lipids to proteins, (2) the fusion of lipoproteins, and (3) the exchange of lipids and proteins between lipoproteins. We are studying the kinetics and thermodynamics of these processes to determine what structural features in the lipid and/or protein are important in the formation of lipoproteins and maintenance of their structural integrity. The enthalpy of association of apolipoprotein C-III from human plasma very low density lipoprotein with pure and mixed diacylphosphatidylcholines has been studied. Also the kinetics of association of apolipoproteins A-I and A-II from human high density lipoproteins with dimyristoylphosphatidylcholine (DMPC) and DMPC-cholesterol mixtures has been investigated. The results indicate that the physical state of the lipid is of primary importance in regulating the kinetics and enthalpy of apolipoprotein-lipid association. We are extending our kinetic and calorimetric studies to other apolipoproteins (apoC-I, apoc-II, apoC-III) and to more complex lipid systems containing triglycerides, cholesteryl ester, cholesterol and other phospholipids. BIBLIOGRAPHIC REFERENCES: J.D. Morrisett, H.J. Pownall and A.M. Gotto. Interaction of apolipoprotein C-III and phosphatidylcholine vesicles: Dependence of Apoprotein-Phospholipid Complex Formation on Vesicle Structure. Biochem. Biophys. Acta. 486: 35-46, 1977. H.J. Pownall, J.D.Morrisett, and A.M. Gotto. Composition-Structure-Function Correlations in the Binding of Apolipoprotein to Phosphatidylcholine Bilayer Mixtures. J. Lipid Res. 18: 14-23, 1977.